Sean W. Flynn

Abnormalities of myelination in schizophrenia detected in vivo with MRI, and post-mortem with analysis of oligodendrocyte proteins.

Schizophrenia unfolds during the late period of brain maturation, while myelination is still continuing. In the present study, we used MRI and T2 relaxation analysis to measure the myelin water fraction in schizophrenia. In schizophrenia (n=30) compared with healthy subjects (n=27), overall white matter showed 12% lower myelin water fraction (P=0.031), with the most prominent effects on the left genu of the corpus callosum (36% lower, P=0.002). The left anterior genu was affected in both first-episode (P=0.035) and chronic patients (P=0.011). In healthy subjects, myelin water fraction in total white matter and in frontal white matter increased with age, and with years of education, indicating ongoing maturation. In patients with schizophrenia, neither relation was statistically significant. Post-mortem studies of anterior frontal cortex demonstrated less immunoreactivity of two oligodendrocyte-associated proteins in schizophrenia (2′,3′-cyclic nucleotide 3′-phosphodiesterase by 33%, P=0.05; myelin-associated glycoprotein by 27%, P=0.14). Impaired myelination in schizophrenia could contribute to abnormalities of neural connectivity and persistent functional impairment in the illness.

Methamphetamine use: a comprehensive review of molecular, preclinical and clinical findings.

Methamphetamine (MA) is a highly addictive psychostimulant drug that principally affects the monoamine neurotransmitter systems of the brain and results in feelings of alertness, increased energy and euphoria. The drug is particularly popular with young adults, due to its wide availability, relatively low cost, and long duration of psychoactive effects. Extended use of MA is associated with many health problems that are not limited to the central nervous system, and contribute to increased morbidity and mortality in drug users. Numerous studies, using complementary techniques, have provided evidence that chronic MA use is associated with substantial neurotoxicity and cognitive impairment. These pathological effects of the drug, combined with the addictive properties of MA, contribute to a spectrum of psychosocial issues that include medical and legal problems, at-risk behaviors and high societal costs, such as public health consequences, loss of family support and housing instability. Treatment options include pharmacological, psychological or combination therapies. The present review summarizes the key findings in the literature spanning from molecular through to clinical effects.

Violence in treatment resistant psychotic inpatients

This study sought to: a) ascertain the effect on rates of violence by varying its operational definition and b) compare characteristics of violent and nonviolent patients. Aggressive behavior was recorded daily for every patient (N = 78) during a 2-year period. Standardized rating scales were used to rate psychopathology and functioning. Almost two thirds of patients were aggressive to others, and 26% violently assaulted another person. Official incident reports underestimated rates of violence to others, self- harm, and property damage. Multivariate predictive models that greatly improved accuracy over base rates showed that violent patients tended to be female, schizophrenic (nonparanoid type), and abusive of alcohol before admission. Violence is more common in treatment resistant psychotic inpatients than suggested by incident reports. Standardized definitions of violence are urged in order to accurately study its prevalence and correlates. Models combining both historical/demographic and clinical data may enhance prediction of violence.

The assessment of symptom severity and functional impairment with DSM-IV axis V.

OBJECTIVE The Global Assessment of Functioning scale (GAF) is included as axis V in the DSM-IV multiaxial diagnostic system. The GAF is simple to administer and routinely used in treatment planning and as a measure of program performance. The GAF assesses both symptom severity and functional impairment, but the resultant rating provides no information about the contribution of each of these domains. This study aimed to improve the clinical utility of the GAF by creating subscales. METHODS The authors divided the scale into its two principal domains: descriptors of social and occupational functioning (SOFAS) and descriptors of symptoms (GAF minus SOFAS descriptors). These and other measures of symptoms and functioning were used to assess 407 patients while acutely psychotic and again after treatment. RESULTS Symptom scores were of greater severity than functional impairment scores in most cases. Because of this, the GAF score tended to reflect symptom severity rather than functional impairment. The symptom rating was more strongly correlated with measures of positive symptoms, and the functional rating had higher associations with negative symptoms and functional impairment. Both scales were good indicators of clinical change. CONCLUSIONS Findings indicate that GAF ratings for patients with psychosis tend to reflect symptom severity rather than functional impairment. Splitting the GAF into two parts resulted in greater discrimination for this patient group yet retained ease of administration.

The incidence of schizophrenia in European immigrants to Canada

OBJECTIVE The risk for schizophrenia in immigrants to Europe is approximately three times that of native-born populations. Discrimination and marginalization may influence the risk for schizophrenia within migrant populations. The primary objective of the present study was to determine whether the risk associated with migration was also evident 100 years ago. A second objective was to determine whether changing social stresses are associated with changes to the incidence of schizophrenia. METHOD During the first two decades of the twentieth century, the Provincial Mental Hospital was the sole provider of psychiatric services in British Columbia, Canada. Detailed clinical records have been preserved for 99.5% of 2477 patients who had a psychiatric admission between 1902 and 1913. Diagnoses were made after a detailed file review and 807 patients met DSM-IV criteria for first-episode schizophrenia, schizophreniform disorder, schizoaffective disorder, or psychosis not otherwise specified. Diagnoses had high inter-rater reliability. The incidence of schizophrenia in migrants from Britain or Continental Europe was compared with that in the Canadian-born population using indirect standardization and Poisson models. RESULTS Migration from Britain or Continental Europe to Canada in the early twentieth century was associated with an increased rate of schizophrenia; IRR=1.54, (95% CI=1.33-1.78). Incidence increased over time in immigrants but not in the native-born population and this increase occurred during a period of economic recession. CONCLUSIONS Migration was a risk factor for schizophrenia a century ago as it is today. This risk occurred in white migrants from Europe and increased during a period of increased social stress.

Low birthweight in schizophrenia: prematurity or poor fetal growth?

In the general population, low birthweight (LBW) is associated with neurological and psychological problems during childhood and adolescence. LBW may result from premature birth or poor fetal growth, and the independent effects of these two events on childhood development are not fully understood. The rate of low weight births is increased in schizophrenia and is associated with social withdrawal during childhood and an early onset of illness. However, it is unclear whether this LBW reflects poor fetal growth or premature birth, or whether these two risk factors have distinct implications for childhood functioning and age at onset of schizophrenia. Subjects included 270 patients with schizophrenia for whom a detailed history of obstetric events could be obtained. The rate of low weight births was high and was associated with poorer premorbid functioning and an earlier age at illness onset. The rate of both premature births and poor fetal growth was high relative to the normal population. Prematurity, but not poor fetal growth, was associated with premorbid social withdrawal and an early age at illness onset. Poor fetal growth, but not prematurity, was associated with low educational achievement. These results suggest that poor fetal growth and prematurity are associated with distinct patterns of childhood maladjustment in individuals who develop schizophrenia.

Predictors of starting to smoke cigarettes in patients with first episode psychosis.

INTRODUCTION Cigarette smoking is common in psychotic disorders and may be initiated in an attempt to control features of illness. However, genetic, obstetric and early life conditions are risks for starting to smoke in the general population but their role in psychotic patients is unclear. METHOD Smoking history and the putative predictors of starting to smoke were assessed in a community-wide sample of 115 first episode psychosis patients. The proportion that initiated smoking was compared with that from population surveys and the impact of risk factors was assessed within the patient sample. RESULTS Most patients began smoking before illness onset and the proportion who initiated smoking was significantly high by the onset of a functional decline. Gestational tobacco exposure was a risk for smoking and was also associated with low birthweight, poor academic achievement, and obesity. Low familial socioeconomic position but not familial psychiatric problems also predicted smoking initiation. DISCUSSION In most cases, smoking preceded illness onset and was not a response to early features of illness. General population predictors of starting to smoke were also associated with smoking initiation in psychotic patients. Of these risks, exposure to tobacco during gestation is noteworthy in that it affects brain development and is associated with cognitive, behavioral, psychiatric and general health problems. In addition, nicotine interacts with other substances of abuse. The initiation of smoking before illness onset and the association with developmental problems raises the question of whether cigarette smoking influences some aspects of illness in patients with psychosis.

Schizencephaly associated with psychosis

Schizencephaly is a rare disorder of brain development resulting in the formation of abnormal unilateral or bilateral clefts in the cerebral hemispheres. It is often accompanied by partial seizures, mental retardation, and hemiparesis. Two patients are described with clear psychotic symptoms with either unilateral or bilateral schizencephaly. The implications of the association between schizencephaly and psychosis in these patients for understanding the biology of the psychoses are discussed.

Symptom changes in five dimensions of the Positive and Negative Syndrome Scale in refractory psychosis

AbstractRefractory psychosis units currently have little information regarding which symptoms profiles should be expected to respond to treatment. In the current study, we provide this information using structural equation modeling of Positive and Negative Syndrome Scale (PANSS) ratings at admission and discharge on a sample of 610 patients admitted to a treatment refractory psychosis program at a Canadian tertiary care unit between 1990 and 2011. The hypothesized five-dimensional structure of the PANSS fit the data well at both admission and discharge, and the latent variable scores are reported as a function of symptom dimension and diagnostic category. The results suggest that, overall, positive symptoms (POS) responded to treatment better than all other symptoms dimensions, but for the schizoaffective and bipolar groups, greater response on POS was observed relative to the schizophrenia and major depression groups. The major depression group showed the most improvement on negative symptoms and emotional distress, and the bipolar group showed the most improvement on disorganization. Schizophrenia was distinct from schizoaffective disorder in showing reduced treatment response on all symptom dimensions. These results can assist refractory psychosis units by providing information on how PANSS symptom dimensions respond to treatment and how this depends on diagnostic category.

Surface shape analysis with an application to brain surface asymmetry in schizophrenia

Some methods for the statistical analysis of surface shapes and asymmetry are introduced. We focus on a case study where magnetic resonance images of the brain are available from groups of 30 schizophrenia patients and 38 controls, and we investigate large-scale brain surface shape differences. Key aspects of shape analysis are to remove nuisance transformations by registration and to identify which parts of one object correspond with the parts of another object. We introduce maximum likelihood and Bayesian methods for registering brain images and providing large-scale correspondences of the brain surfaces. Brain surface size-and-shape analysis is considered using random field theory, and also dimension reduction is carried out using principal and independent components analysis. Some small but significant differences are observed between the the patient and control groups. We then investigate a particular type of asymmetry called torque. Differences in asymmetry are observed between the control and patient groups, which add strength to other observations in the literature. Further investigations of the midline plane location in the 2 groups and the fitting of nonplanar curved midlines are also considered.